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MGMT 表达对低级别神经节胶质瘤预后的影响:一项临床病理和免疫组织化学研究。

The prognostic impact of MGMT expression on low-grade gangliogliomas: a clinicopathological and immunohistochemical study.

机构信息

Chih-Hsin Hung, PhD, Institute of Biotechnology and Chemical Engineering, I-Shou University, No. 1, Sec. 1, Syuecheng Rd., Dashu District, Kaohsiung City 84001, Taiwan, phone: 886-7-657-7711 ext. 3414, fax: 886-7-615-0974, e-mail:

出版信息

Folia Neuropathol. 2013;51(4):275-82. doi: 10.5114/fn.2013.39716.

Abstract

Ganglioglioma (GG) is an uncommon brain parenchymal neoplasm. Although most cases have indolent clinical behaviour, a subgroup of GGs does recur, especially in patients with unresectable disease. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients with malignant glioma treated with alkylating agents. Furthermore, MGMT promoter methylation has also been investigated as an independent favourable prognostic factor for glioblastoma. The primary management is surgical resection for GGs and gross total resection is recommended. Despite infrequent use of chemotherapy for low-grade GGs, it was still introduced to a subset of patients, especially those who had unresectable disease. We assessed clinicopathological features of nine cases of low-grade GG to further elucidate the relationship between the status of the MGMT protein expression and the prognosis. This series included four men and five women with a mean age of 21.6 years at the first surgery. The mean postoperative follow-up period was 6 years. Only two patients had recurrent disease after 1.7 and 3.2 years of the first surgery. Immunohistochemically, 11.1% exhibited 3+ nuclear staining for MGMT protein, 11.1% exhibited 2+ staining, 33.3% exhibited 1+ staining, and 44.4% exhibited 0 staining. Tumours with more intensive MGMT protein expression (2+~3+ immunostaining) tended to recur more frequently (p < 0.05), corresponding to the worse prognostic predictive value of intensive MGMT staining.

摘要

神经节神经胶质瘤(GG)是一种罕见的脑实质肿瘤。尽管大多数病例具有惰性的临床行为,但有一小部分 GG 确实会复发,尤其是在无法切除疾病的患者中。O6-甲基鸟嘌呤 DNA 甲基转移酶(MGMT)是一种 DNA 修复蛋白,可从 DNA 中的 O6-鸟嘌呤中去除致突变和细胞毒性加合物。免疫组化缺乏 MGMT 蛋白表达与接受烷化剂治疗的恶性神经胶质瘤患者的药物反应有关。此外,MGMT 启动子甲基化也被研究为胶质母细胞瘤的独立有利预后因素。主要治疗方法是手术切除 GG,推荐进行大体全切除。尽管低级别 GG 很少使用化疗,但仍将其引入了一部分患者,尤其是那些无法切除疾病的患者。我们评估了 9 例低级别 GG 的临床病理特征,以进一步阐明 MGMT 蛋白表达状态与预后之间的关系。该系列包括 4 名男性和 5 名女性,第一次手术时的平均年龄为 21.6 岁。平均术后随访时间为 6 年。仅 2 例患者在第一次手术后 1.7 年和 3.2 年复发。免疫组化结果显示,MGMT 蛋白的核染色为 3+的占 11.1%,2+的占 11.1%,1+的占 33.3%,0 染色的占 44.4%。MGMT 蛋白表达更强(2+~3+免疫染色)的肿瘤更倾向于频繁复发(p<0.05),这对应于密集 MGMT 染色的预后预测价值更差。

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